4-(3- and 4-Chlorocyclohex-3-enyl)pyridine intermediates

ABSTRACT

4-(3- and 4-chlorocyclohex-3-enyl)pyridines, useful as intermediates in the preparation of pesticides and bactericides, are prepared by reacting a 4-vinylpyridine with chloroprene.

This application is a division of application Ser. No. 300,046, filedSept. 8, 1981, now U.S. Pat. No. 4,405,792 issued Sept. 20, 1983.

This invention relates to the preparation of 4-(3- or4-halophenyl)pyridines and to novel intermediates for the synthesis ofsuch compounds.

BACKGROUND

A three-step synthesis of 4-phenyl pyridine from alphamethyl styrene,formaldehyde and ammonium chloride has been reported by Schmidle andMansfield, J. Am. Chem. Soc., 78, 1702-1705 (1956). In that process thereactants are condensed to form 6-methyl-6-phenyltetrahydro-1,3-oxazine.This is converted with excess acid to4-phenyl-1,2,3,6-tetrahydropyridine which in turn is dehydrogenated to4-phenyl pyridine using nitrobenzene and palladium catalyst. The authorspoint out both in the foregoing paper and in U.S. Pat. No. 2,847,414that this dehydrogenation reaction can be effected in the presence orabsence of a hydrogen acceptor such as nitrobenzene. The patentindicates that the dehydrogenation should be conducted at temperaturesbetween 125° and 220° C.

The condensation of 4-vinyl pyridine with diene hydrocarbons has beendescribed by Petrov and Lyudvig, The Journal of General Chemistry of theU.S.S.R., Volume 26, January 1956 (English Translation Copyright 1956),Consultants Bureau, Inc., New York, N.Y., pages 49-51. The authorsinvestigated the reaction of 4-vinyl pyridine with butadiene,piperylene, isoprene, diisopropenyl and cyclopentadiene. All thesubstances, apart from that prepared from cyclopentadiene, weresubjected to dehydrogenation over palladium. The resultant arylpyridineswere isolated in the form of picrates.

The use of chloroprene in Diels-Alder reactions with acrylic acid orstyrene is reported by Titov and Kuznetsova, Bulletin of the Academy ofSciences USSR, Division of Chemical Sciences (English Translation, 1960,page 1687).

In order to synthesize halophenylpyridines, previous workers haveresorted to reactions between a diazonium salt and a pyridine. See inthis connection Butterworth, Heilborn and Hey, J. Chem. Soc., 1940,355-358 and Netherlands Application No. 6,414,307, June 11, 1965[Chemical Abstracts, 64 713d (1966)]. In these procedures, mixed isomersare formed and thus in order to recover the individual isomers inrelatively pure form, recourse was had to such separation techniques asfractional crystallization and column chromatography.

It is known that aryl halogen atoms can be removed by hydrogen in thepresence of a noble metal catalyst such as palladium. See H. O. House,Modern Synthetic Reactions, 2nd Edition, W. A. Benjamin Publishers,Copyright 1972, page 14.

THE INVENTION

It has now been found that:

(a) Novel compounds, viz., 4-(3- or 4-chlorocyclohex-3-enyl)pyridines,can be prepared by reacting a 4-vinyl pyridine with chloroprene underconditions whereby a Diels-Alder-type condensation occurs; and

(b) 4-(3- or 4-chlorophenyl)pyridines can be prepared by catalyticallydehydrogenating a 4-(3- or 4-chlorocyclohex-3-enyl)pyridine in thepresence of a suitable hydrogen acceptor.

Thus, in accordance with one embodiment of this invention there isprovided a process for the preparation of 4-chlorophenyl)-pyridines inwhich the chlorine atom is in the 3- or 4-position of the phenyl groupwhich comprises reacting a 4-vinyl pyridine with chloroprene to form a4-(3- or 4-chlorocyclohex-3-eenyl)-pyridine (usually a mixture of theseisomers is formed) and then catalytically dehydrogenating the 4-(3- or4-chlorocyclohex-3-enyl)-pyridine to form a 4-(3- or4-chlorophenyl)pyridine. Preferably a mixture of4-(3-chlorocyclohex-3-enyl)pyridine and4-(4-chlorocyclohex-3-enyl)pyridine is subjected to this catalyticdehydrogenation. It is possible, however, to separate these isomers, forexample by selective crystallization techniques or the like, andthereupon subject either isomer to the catalytic dehydrogenation.

The reactions of this invention may be depicted as follows: ##STR1## Inthese equations R₁, R₂, R₃ and R₄ are, independently, hydrogen orinnocuous substituents, and one of R₅ and R₆ is chlorine and the otheris hydrogen. Exemplary innocuous substituents, i.e., substituents whichordinarily do not prevent the designated reaction from taking place norpromote excessive decomposition of the desired product include loweralkyl, aryl, aralkyl, cycloalkyl, haloalkyl, haloaryl, ring-haloaralkyl,alkoxy and aryloxy, halo substituents (i.e., fluoro, chloro and bromo),nitrogen containing heterocyclic groups, and the like.

Other embodiments of this invention include the condensation processitself, the novel products formed in the condensation process, and thedehydrogenation process itself. These and other embodiments of theinvention will be still futher apparent from the ensuing description andappended claims.

CONDENSATION PROCESS

Reaction temperatures in the range of about 50° to about 250° C. andpreferably in the range of about 100° to about 150° C. are recommended.

Although it is possible to conduct the reaction in the absence of anadded solvent, it is preferable to use a reaction diluent. Among thesolvents which may be used for this process are aromatic hydrocarbons,paraffinic hydrocarbons, cycloparaffinic hydrocarbons, aliphatichalohydrocarbons, aromatic halohydrocarbons, ethers, esters and thelike. Naturally, the solvent selected should exist in the liquid stateat the reaction temperature employed.

The proportions as between the 4-vinyl pyridine reactant and thechloroprene can be varied to a considerable extent. Ordinarily, it willbe found desirable to employ the reactants in a molar ratio(chloroprene:4-vinyl pyridine reactant) in the range of from about 0.5:1up to about 10:1 and preferably in the range of about 0.75:1 to about2:1.

The condensation reaction is not particularly rapid and accordinglyreaction periods ranging from about 0.25 to about 20 hours are generallyfound most satisfactory.

For best results, the reaction should be performed in a closed reactionsystem such as a pressure-resistant autoclave. Desirably, the reactionshould be performed under an inert atmosphere so as to minimize the sidereactions such as polymerization and the like. In order to furtherminimize polymer formation, it is possible to introduce either or bothof the reactants into the heated reaction system on an incrementalbasis. Polymerization inhibitors such as phenothiazine, oxygen, phenolicor aromatic amino compounds and the like may be added. In this way, thedesired Diels-Alder-type condensation reaction in favored-overcompetitive polymerization reactions.

This condensation process gives rise to the formation of novel products,viz., 4-(chlorocyclohex-3-enyl)pyridines of the formula ##STR2## whereinR₁, R₂, R₃ and R₄ are, independently, hydrogen, or innocuoussubstituents (see above) and wherein one of R₅ and R₆ is chlorine andthe other is hydrogen.

To recover these products from the reaction mixture, it may be desirableto utilize extraction procedures rather than distillation. For example,use of aqueous acidic extraction procedures such as set forth in theexamples hereinafter enables isolation of the pyridine derivatives fromthe balance of the reaction mixture. Other workup procedures may proveuseful such as fractional crystallization, column chromatography, andthe like. The isolated products may be further purified by distillation.

As noted above--see Equation (I)--the process is applicable to a varietyof suitably substituted 4-vinyl pyridines. Illustrative compounds foruse in this reaction include 2-methyl-4-vinylpyridine,2,3-dimethyl-4-vinylpyridine, 3-ethyl-4-vinylpyridine,2,3,5,6-tetramethyl-4-vinylpyridine, 2-phenyl-4-vinylpyridine,2-(2-pyridyl)-4-vinylpyridine, 2-chloro-4-vinylpyridine,3-trifluoromethyl-4-vinylpyridine, 3,5-diethoxy-4-vinylpyridine,2-(2-tetrahydrofuranyl)4-vinylpyridine, and the like.

Use of 4-vinyl pyridine itself is most preferred pursuant to thisinvention.

DEHYDROGENATION PROCESS

In this process, 4-(chlorophenyl)pyridines in which the chlorine is inthe 3- or 4-position are produced by heating 4-(3- or4-chlorocyclohex-3-enyl)pyridine with a dehydrogenation catalyst in theprocess of a hydrogen acceptor to a dehydrogenation temperature so thatthe desired product is formed. A feature of the process is that thecyclohexenyl ring is aromatized without concommitant loss of chlorinefrom the chlorophenyl product.

As noted above, it is preferred to employ a mixture of4-(3-chlorocyclohex-3-enyl)pyridine and4-(4-chlorocyclohex-3-enyl)-pyridine in this process as this enables useof the mixed isomer product as formed in the condensation process. Whenusing such mixtures, the resultant 4-(chlorophenyl)pyridine will be amixture of the 3-chlorophenyl and 4-chlorophenyl isomers. However, thearomatization process of this invention may be applied to either of theabove-individual 4-(chlorocyclohex-3-enyl)pyridine isomers, i.e., the3-chloro isomer or the 4-chloro isomer.

The catalyst used in the process is preferably a palladium catalyst. Thecatalyst may be employed in various physical forms, for example, it maybe supported on alumina or other suitable carrier. A catalyst composedof palladium on carbon has been found particularly useful in theprocess. Normally, the catalyst will be used in particulate orsubdivided form. Quantities ranging from about 0.1 to about 50 weightpercent--preferably 1 to 10 weight percent--based on the weight of the4-(chlorocyclohex-3-enyl)pyridine being aromatized are generally usedalthough departures from these ranges are permissible.

Hydrogen acceptors suitable for use in the process includedinitrobenzenes; nitroalkanes such as nitroethane; alkenes such asethylene and propylene; substituted quinones; and the like. Nitrobenzeneand its congeners are preferred for use in the process. For bestresults, the hydrogen acceptor should be in the liquid phase in thereaction system under the reaction conditions being employed.

The relative proportions as between the 4-(3- or4-chlorocyclohex-3-enyl)pyridine and the hydrogen acceptor can be variedto a considerable extent, provided of course, there is a sufficientamount of the hydrogen acceptor to perform its desired function in thereaction system. Ordinarily, enough hydrogen acceptor is added to absorball of the hydrogen from the aromatization. A particularly convenientmethod of operation is to use the hydrogen acceptor as the solvent andthus very substantial excesses may be used.

Exemplary 4-(chlorocyclohex-3-enyl)pyridines for use in this processinclude 4-(4-chlorocyclohex-3-enyl)-3-methylpyridine,4-(4-chlorocyclohex-3-enyl)-2-propoxypyridine,4-(3-chlorocyclohex-3enyl)-2-(4-tolyl)pyridine,4-(4-chlorocyclohex-3-enyl)-2,6-dimethylpyridine,4-(3-chlorocyclohex-3-enyl)-2-6-dichloropyridine, and the like.Particularly preferred are 4-(4-chlorocyclohex-3-enyl)pyridine and4-(3-chlorocyclohex-3-enyl)pyridine, and mixtures thereof.

Reaction temperatures generally fall within the range of about 100° toabout 300° C. and are selected in any given case to achieve a suitablerate of dehydrogenation without incurring an undesired amount ofdechlorination. In short, the dehydrogenation temperature employed isone at which the 4-(3- or 4-chlorocyclohex-3-enyl)pyridine isdehydrogenated so that a 4-(3- or 4-chlorophenyl)pyridine is formed.

The 4-(3- or 4-chlorocyclohex-3-enyl)pyridine, dehydrogenation catalyst,and hydrogen acceptor should be heated in contact with each other for asufficiently long period for the desired aromatization to take place.Reaction periods ranging from about 0.25 to about 40 hours are generallymost satisfactory although, of course, the length of the reaction periodmay be affected to some extent by the quantity and activity of thecatalyst and by the reaction temperature being employed.

If desired, the reaction mixture may include an inert solvent ordiluent.

Workup procedures involving extraction techniques, fractionalcrystallization, distillation and column chromatography have been founduseful.

The practice of this invention will be still further apparent from thefollowing illustrative examples.

EXAMPLE I

A stainless steel bomb was charged with a performed mixture of 30 g (286mmoles) of 4-vinyl pyridine, 76 g of a 50 percent chloroprene solution[i.e., 37.9 g (429 mmoles) of chloroprene], 15 ml of xylene, and 0.33 g(1.4 mmoles) of 2,6-di-tert-butyl-p-cresol antioxidant. The reactionmixture was heated by means of an oil bath at 150°-160° C. for tenhours. The pressure within the sealed bomb remained below 100 psi. Afterten hours, the contents of the bomb were gradually allowed to cool toroom temperature. The reaction mixture, a rather thick slurry of tancolored material, was removed from the bomb by means of methylenechloride. A portion of the resultant mixture was extracted with aqueousHCl, followed by neutralization. Analysis of the resultant oil by gaschromatography and NMR spectroscopy showed that most of the vinylpyridine was consumed and that three major new products were formed,presumably including 4-(3- and 4-chlorocyclohex-3-enyl)pyridines.

EXAMPLE II

A mixture of 4-vinyl pyridine (20 g) and chloroprene (20 ml of a 50weight percent solution in xylene) was heated in a sealed tube equippedwith a pressure gauge for 20 hours at 160°-165° C. No significantpressure change occurred--the pressure rose by about 20 psi. At the endof the 20-hour reaction period, the reaction mixture, which initiallycontained the reactants in a molar ratio of 1:2 (chloroprene to 4-vinylpyridine), was transferred to a separatory funnel and extracted threetimes with 1N HCl (50 ml portions). The organic layer was discarded. Theaqueous layer was then treated with 50 percent aqueous sodium hydroxidesolution until the pH was approximately 10. This mixture was thenextracted with methylene chloride three times (50 ml portions) and thecombined methylene chloride layers dried with potassium carbonate. Thedried methylene chloride mixture was then filtered and the filtrate wasquickly evaporated using a rotary evaporator followed by a vacuum pumpleaving about 13 g of an oily residue. Analysis by gas chromatographyindicated the presence of only two major products. This oily residue wastaken up in diethyl ether yielding a milky solution from which a whitishprecipitate settled. The ether layer was collected and evaporated togive approximately 10 g of an oily product which still contained twomajor products as indicated by gas chromatography. The residue wasdistilled at 15 mm pressure at about 60°-65° C. to remove any residual4-vinyl pyridine. The residue was further distilled at 110°-120° C. at0.3 mm pressure yielding two fractions, the first of which(approximately 3 g) contained the two major products. This fraction wasseparated into two products by means of thin layer chromatography usingsilica gel and diethyl ether solvent. NMR spectoscopy indicated that oneof these products was probably a dimer of 4-vinyl pyridine. The otherproduct, the major component in the system, was identified to be amixture of 4-(3- and 4-chlorocyclohex-3-enyl)-pyridines with theassistance of carbon and proton NMR spectroscopy.

EXAMPLE III

A mixture of 170 mg of the 4-(3- and 4-chlorocyclohex-3-enyl)pyridinesproduced in Example II, 20 mg of 5 percent palladium on carbon, and oneml of nitrobenzene was stirred under nitrogen for three hours at 120° C.High pressure liquid chromatography indicated that no appreciablereaction had occurred under these conditions. Thus, the same reactionmixture was heated to 225° C. and the refluxing mixture maintained undernitrogen. Periodic inspection of the reaction mixture by means of highpressure liquid chromatography showed that by the end of six hours asignificant quantity of 4-(chlorophenyl)pyridines had been formed. Inthis six hour reaction period, the reaction proceeded to about 80percent completion. After cooling to room temperature, the crudereaction mixture was partitioned between chloroform (50 ml) and 1N HCland the chloroform layer extracted several times with 1N HCl. The darklycolored combined aqueous layer was treated with a small quantity ofactivated charcoal, heated with stirring for ten minutes and filtered.The filtrate, no longer dark in color, was neutralized with sodiumhydroxide to a pH of about 10 and again extracted with chloroformseveral times. The chloroform layers were combined, dried and evaporatedto give 15 mg of a black residue. This residue was taken in a smallamount of methanol and the methanol solution subjected to high pressureliquid chromatography which indicated the presence of 4-(3- and4-chlorophenyl)pyridine. Identification was assisted by comparison with4-(4-chlorophenyl)pyridine prepared by an independent route.

EXAMPLE IV

A mixture of 200 mg of 4-(3- and 4-chlorocyclohex-3-enyl)pyridinesprepared in Example II, 30 mg of 5 percent palladium on carbon, and oneml of acetophenone was heated at 225° C. for four hours under nitrogenatmosphere. High pressure liquid chromatography showed that no producthad been formed under these conditions, thus indicating acetophenone isnot an efficient hydrogen acceptor for use in the process. Thereupon,about 0.5 ml of nitrobenzene was added to this mixture and then heatingcontinued at 225° C. Shortly thereafter, the process was found by meansof high pressure liquid chromatography to have proceeded to about 50percent completion with the resultant formation of 4-(3- and4-chlorophenyl)pyridines along with other by-products.

EXAMPLE V

A mixture of 4-vinyl pyridine (5 ml) and chloroprene (15 ml of a 50percent by weight solution in xylene) was heated in a sealedpolytetrafluoroethylene reactor (20 ml capacity) for ten hours at125°-130° C. In this reaction the initial molar ratio was about 1.6:1(chloroprene:4-vinyl pyridine). The resultant reaction mixture wasyellowish in color and contained some solid materials. Unreacted 4-vinylpyridine and chloroprene, and xylene solvent were evaporated off, andthe residue taken up in methanol and filtered. The filtrate was againevaporated yielding a reddish oil which was taken up in methylenechloride and extracted three times with 2N HCl (100 ml portions). Thecombined HCl washings were shaken thoroughly with three separateportions of diethyl ether (50 ml each) and the HCl layer was thenneutralized with sodium hydroxide to a pH of about 12. A dark colorproduct separated and this was extracted with methylene chloride.Evaporation of the methylene chloride left a reddish liquid which afterpumping on a vacuum pump gave 3.5 g of a crude product. NMR spectraindicated that the major components in this product were the 4- (3- and4-chlorocyclohex-3-enyl)pyridines.

EXAMPLE VI

By refluxing 150 mg of 4-(3- and 4-chlorocyclohex-3-enyl)-pyridinesproduced in Example II with 10 mg of 5 percent palladium on carbon innitrobenzene at 225° C. for 5 hours, the reaction was shown by highpressure liquid chromatography (HPLC) to have gone to 50 percentcompletion. The nitrobenzene was removed by steam distillation, theresidue was partitioned between methylene chloride and water, and theorganic layer was dried and evaporated to give a darkly colored productcontaining 4-(3- and 4-chlorophenyl)pyridines.

EXAMPLE VII

A mixture of 80 mg of 4-(3- and 4-chlorocyclohex-3-enyl)-pyridinesproduced in Example II, one ml of nitrobenzene and 20 mg of 5 percentpalladium on carbon was refluxed at 145°-150° C. and 80 mm pressure for4 hours. HPLC indicated no reaction had occurred under these conditions.By heating the mixture at 170°-180° C. at atmospheric pressureovernight, a small conversion (less than 10 percent) to the desired4-(3- and 4-chlorophenyl)-pyridine product occurred.

EXAMPLE VIII

A condensation reaction was performed by heating 2.5 ml of 4-vinylpyridine, 10 ml of chloroprene and 50 mg of 2,6-di-tert-butyl-p-cresolantioxidant at 125°-130° C. for 10 hours. The liquid reaction product,which contained a ball of rubbery polymer, was taken up in methanol.Evaporation of the methanol left an oily residue. This was taken up indiethyl ether and extracted three times with 6N HCl (total 100 ml). Theaqueous layer was neutralized with aqueous sodium bicarbonate to pH 7.The product was then extracted three times with chloroform (100 mlportions). The chloroform solutions were combined, dried and evaporatedto give 1.3 g of an oil which was indicated by gas chromatography tocontain only two products, viz., the desired 4-(3- and4-chlorocyclohex-3-enyl)pyridines in the ratio of 76:24, respectively.

EXAMPLE IX

A mixture of 130 mg of the 4-(3- and 4-chlorocyclohex-3-enyl)pyridineproduced in Example II, 50 mg of acetic acid, 10 mg of 5 percentpalladium on carbon and one ml of nitrobenzene was stirred for 4 hoursat 120° C. High pressure liquid chromatography revealed that no reactionhad occurred to this point. Then the mixture was heated at 190° C. and150 mm pressure for 6 hours. HPLC indicated that to this point only asmall conversion (about 2 percent) to the desired product had takenplace. Thereupon, the mixture was heated at 225° C. at atmosphericpressure for 8 hours. The HPLC analysis of this crude reaction productshowed it to be a 50:50 mixture of starting material and reactionproducts. The crude reaction mixture was taken in ether and solidsfiltered off. The ether solution was extracted three times with 50 mlportions of 1N HCl. The aqueous layers were combined, washed twice withether (50 ml portions), neutralized with aqueous KOH to pH of about 10,and extracted with ether. The ether solution was then dried, filteredand evaporated to give about 100 mg of a reddish oil containing, interalia, the desired 4-(3- and 4-chlorophenyl)-pyridines.

EXAMPLE X

A mixture of 1.5 ml of 4-vinyl pyridine, 6 ml of a 50 percent by weightsolution of chloroprene in xylene, 12 ml of xylene and 30 mg of2,6-di-tert-butyl-p-cresol antioxidant was heated at 125°-130° C. in asealed polytetrafluoroethylene reactor for 10 hours. The reactionmixture was taken up in ether and extracted with 6N HCl (3 times; 20 mlportions) to give a pale yellowish aqueous layer. This layer was furtherwashed with ether and then neutralized with aqueous potassium hydroxidesolution to pH 8. This was then extracted with chloroform (4 times;about 100 ml portions). The organic layer was cloudy and was againwashed with water and then with saturated saline solution, dried andevaporated to give about 1.2 g of an oily product. Analysis by gaschromatography showed that the major product was the desired 4-(3- and4-chlorocyclohex-3-enyl)pyridines, together with unreacted startingmaterials. Volatiles were stripped from this oily product by means of avacuum pump yielding as residue 0.7 g of a reddish orange oil, whichconsisted mostly of the desired product (i.e., the foregoing twochlorocyclohex-3-enyl isomers). The yield of this product was estimatedto be about 30-40 percent based on the amount of stirring material usedand the purity of the product as indicated by gas chromatography.

EXAMPLE XI

A reaction mixture composed of 100 mg of 4-(3- and4-chlorocyclohex-3-enyl)pyridines, 10 mg of 5 percent palladium oncarbon and 2 ml of dodecene was heated under a nitrogen atmosphere at240° C. for 6 hours. This gave only a 2 percent conversion to thedesired product based on HPLC analysis.

EXAMPLE XII

A mixture of 210 mg of 4-(3- and 4-chlorocyclohex-3-enyl)-pyridine, 20mg of 5 percent palladium on carbon and 2 ml of nitrobenzene wasrefluxed for 8 hours at 240° C. under a nitrogen atmosphere. HPLC showedthat under these conditions all of the starting material had reacted andthus the conversion to reaction product was at least 98 percent. Thecrude mixture was taken up in ether, extracted with 1N HCl (3extractions; 50 ml each) and the aqueous layer neutralized with aqueousKOH solution. The organic phase was again extracted with ether (3 times;50 ml each) and the combined layers dried with potassium carbonateovernight. Evaporation of the ether layer gave a reddish orange oil,which when taken up in hexane and treated with a small quantity ofactivated charcoal, became a pale yellow oil. The NMR spectrum of thisproduct showed it to contain the desired 4-(3- and4-chlorophenyl)pyridines, together with unreacted starting material.

EXAMPLE XIII

Heated at 130°-140° C. for 10 hours was a mixture of 1.5 ml of 4-vinylpyridine, 6 ml of 50 percent by weight solution of chlorophene inxylene, 12 ml of xylenes and 150 mg of 2,6-di-tert-butyl-p-cresolantioxidant. The crude reaction mixture was taken up in ether (100 ml)and extracted with 1N HCl (4 times; 50 ml portions). The HCl layer wasthen neutralized with aqueous KOH to a pH of about 10 and extracted withchloroform. The chloroform layer was dried, filtered and evaporatedunder reduced pressure to give an oily product which contained, inaddition to unreacted starting materials and dimer from 4-vinylpyridine, a quantity of the desired 4-(3- and4-chlorocyclohex-3-enyl)pyridines. The ratio of this desired product tothe dimer was about 7:1.

EXAMPLE XIV

Several crude product mixtures from condensation reactions reported inearlier examples herein were combined and distilled at 150°-160° C.(reflux temperature) at low pressure (0.5-0.3 mm). The fractioncollected at these temperatures contained 4-(3- and4-chlorocyclohex-3-enyl)pyridines of a purity of at least about 80percent as shown by gas chromatography. A portion of this distillation(550 mg) was heated with 90 mg of 5 percent palladium on carbon in 5 mlof nitrobenzene for 8 hours at 240° C. The reaction mixture was taken upin methanol (about 5 ml) and this solution was slowly added to 100 ml ofether. The ether layer was filtered, the filtrate was extracted 4 timeswith 1N HCl (50 ml portions) and then the aqueous layer was washed 3times with ether (100 ml portions). The aqueous layer was thenneutralized to a pH of about 9 and again extracted with ether. The etherlayer was dried, filtered and then evaporated to give about 420 mg ofproduct. HPLC indicated that this contained a substantial quantity ofthe desired 4-(3- and 4-chlorophenyl)pyridines. This mixture was takenup in hexane and treated with activated charcoal. After heating themixture to reflux, it was then filtered and the filtrate was evaporatedto give 200 mg of an oil which was shown by NMR spectroscopy to be amixture of the desired 4-(3- and 4-chlorophenyl)pyridines, together withunreacted starting material. The yield of this product was estimatedfrom spectral data to be about 20 to about 25 percent.

EXAMPLE XV

A condensation reaction was performed using 1.5 ml of 4-vinyl pyridine,6 ml of chloroprene (50 percent solution in xylene), 12 ml of xylene and150 mg of 2,6-di-tert-butyl-p-cresol antioxidant. The reactionconditions involved heating for 6 hours at 120°-130° C. Analysis of thecrude reaction mixture indicated that extensive reaction had notoccurred under these conditions. Nevertheless, the crude reactionmixture was taken up in ether and extracted with 1N HCl (3 times; 50 mlportions). Then the aqueous layer was washed with 50 ml portions ofether, neutralized with KOH and extracted with chloroform (3 times; 50ml portions). The chlorform layer was dried, filtered and evaporatedyielding about 0.7 g of an oil which contained mostly unreacted startingmaterials. On further evaporation, the starting materials were strippedoff leaving about 220 mg of an almost colorless oil which contained thedesired 4-(3- and 4-chlorocyclohex-3-enyl)pyridines and a dimer from4-vinyl pyridine in a ratio of 9:1. The conversion in this case was onlyabout 10 percent.

EXAMPLE XVI

A pressure bottle was charged with 10.5 ml of 4-vinyl pyridine, 42 ml ofchloroprene, 84 ml of xylene solvent and 210 mg of2,6-di-tert-butyl-p-cresol antioxidant. This mixture was heated in thesealed bottle for 5 hours at 180°-190° C. The product formed under theseconditions had an excessive rubbery consistency thus indicating thatextensive polymerization had occurred (the initial chloroprene to4-vinyl pyridine molar ratio was 2:1).

EXAMPLE XVII

A sample of 4-(3- and 4-chlorocyclohex-3-enyl)pyridine of a puritygreater than 93 percent, together with 40 mg of 5 percent palladium oncarbon and 5 ml of nitrobenzene was heated under reflux for 15 hours at230°-240° C. At the end of this time the HPLC trace showed that thereaction was essentially complete. The reaction mixture was poured into100 ml of anhydrous ether and the ether solution was filtered. Thefiltrate was extracted 4 times with 1N HCl solution (50 ml portions).The combined aqueous layer was washed twice with 50 ml portions of etherand neutralized to pH 10 with sodium hydroxide solution (50 percent).The product was then extracted several times with hexane and the hexanelayers were combined, dried, treated with a small quantity of activatedcharcoal, and filtered. The treated product (approximately 170 mg) waschromatographed on a 2 mm silica gel plate and eluted with diethylether. This chromatographic procedure was repeated 4 times. The majorband, identified by shining UV light on the plate, was isolated and theorganic material extracted therefrom with a mixture of 5 percentmethanol in chloroform. The chloroform layer was evaporated yieldingabout 127 mg of an oily product. Analysis by gas chromatography showed 3peaks and NMR established the presence of the desired product. A massspectrum revealed that the product contained 4-(3- and4-chlorophenyl)pyridines, together with some 4-vinyl pyridine. The datashowed that the combined yield of 4-(4-chlorophenyl)pyridine and4-(3-chlorphenyl)pyridine was about 30 percent, that the ratio of theseisomers (4-chlorophenyl: 3-chlorophenyl) was 4:1 and the ratio of the4-(3- and 4-chlorophenyl)pyridines to 4-vinyl pyridine was about 19:1.

EXAMPLE XVIII

On heating a mixture of 480 mg of 4-(3- and4-chlorocyclohex-3-enyl)pyridines with 5 percent palladium on carbon at290° C. for about 30 minutes, the reaction product was found to containpredominantly 4-phenyl pyridine. Thus, under these conditions bothdehydrogenation and dechlorination occurred.

EXAMPLE XIX

An attempt was made to aromatize 4-(3- and4-chlorocyclohex-3-enyl)pyridines (180 mg) in a mixture of 20 mg of 5percent palladium on carbon, 5 ml of nitrobenzene and one molarequivalent (based on the para-substituted pyridine reactant) of toluenesulfonic acid. Heating of the product for 6 hours at 220° C. under anitrogen atmosphere yielded a highly complex mixture of productsunworthy of further workup.

EXAMPLE XX

When 240 mg of 4-(3- and 4-chlorocyclohex-3-enyl)pyridines was heatedwith 30 mg of 5 percent palladium on carbon in 10 ml of a mixture oftetradecene in liquid paraffin at 240° C. for 10 hours, HPLC indicatedthat the reaction had not proceeded favorably under these conditions.

EXAMPLE XXI

A pressure autoclave equipped with a stirrer, thermocouple and severalinlet means was charged with 2 g of 4-(3- and4-chlorocyclohex-3-enyl)pyridines, 100 mg of 5 percent palladium oncarbon and 100 ml of hexadecene. One of the inlets to the autoclave wasattached to a source of pressurized ethylene and the autoclavepressurized to 200 psi with ethylene. The sealed autoclave was thenheated to 100° C. and kept there for 3 hours. Analysis of a sample ofthe reaction mixture by HPLC showed that no reaction had occurred.Accordingly, the mixture was heated to 200° C. and kept there for 2hours. HPLC again indicated that no reaction had occurred. Thereupon,the ethylene pressure was increased to 600 psi and the temperatureraised to 300° C. and held there for one hour. In this instance HPLCshowed that a small amount of reaction had occurred.

EXAMPLE XXII

A mixture of 0.5 grams of 4-(3- and 4-chlorocyclohex-3-enyl)pyridines,30 mg of 5 percent palladium on carbon and 20 ml of nitrobenzene washeated in incremental stages. On heating at 100° C. for 2 hours HPLCrevealed no reaction had occurred. Heating at 200° C. for 2 hours againproduced no reaction. On heating at 250° C. reaction was found to havecommenced.

EXAMPLE XXIII

A mixture of 250 mg of 4-(3- and 4-chlorocyclohex-3-enyl)-pyridines, 2ml of p-cymene and 10 mg of 5 percent palladium on carbon was heated at177° C. for 10 hours. Analysis of the product mixture by HPLC showedthat only a low conversion to reaction products had occurred. Thereaction products appeared to be composed of 4-phenyl pyridine and 4-(4-and 3-chlorophenyl)pyridines in approximately equal amounts.

In addition to having the pesticidal properties reported in NetherlandsApplication No. 6,414,307 [Chemical Abstracts, 64, 713d (1966)], the4-(4-chlorophenyl)pyridines and 4-(3-chlorophenyl)-pyridines are usefulintermediates for the synthesis of other biologically active substances,such as for example 1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinolinecarboxylic acid derivatives which are known to have useful antibacterialproperties. Information concerning such derivatives is given in U.S.Pat. Nos. 3,753,993 and 3,907,808, both to Lesher and Carabateas. Thenovel 4-(3- and 4-chlorocyclohex-3-enyl)pyridines of this invention arelikewise useful as intermediates for the synthesis of variousbiologically active substances, including the foregoing phenyl pyridinepesticides and pyridyl quinoline carboxylic acid type antibacterials.

I claim:
 1. In admixture the compounds,4-(4-chlorocyclohex-3-enyl)pyridine and4-(3-chlorocyclohex-3-enyl)pyridine. 2.4-(4-Chlorocyclohex-3-enyl)pyridine. 3.4-(3-Chlorocyclohex-3-enyl)pyridine.